KAT8 beyond Acetylation: A Survey of Its Epigenetic Regulation, Genetic Variability, and Implications for Human Health.

Lysine acetyltransferase 8, also known as KAT8, is an enzyme involved in epigenetic regulation, primarily recognized for its ability to modulate histone acetylation. This review presents an overview of KAT8, emphasizing its biological functions, which impact many cellular processes and range from chromatin remodeling to genetic and epigenetic regulation. In many model systems, KAT8's acetylation of histone H4 lysine 16 (H4K16) is critical for chromatin structure modification, which influences gene expression, cell proliferation, differentiation, and apoptosis. Furthermore, this review summarizes the observed genetic variability within the KAT8 gene, underscoring the implications of various single nucleotide polymorphisms (SNPs) that affect its functional efficacy and are linked to diverse phenotypic outcomes, ranging from metabolic traits to neurological disorders. Advanced insights into the structural biology of KAT8 reveal its interaction with multiprotein assemblies, such as the male-specific lethal (MSL) and non-specific lethal (NSL) complexes, which regulate a wide range of transcriptional activities and developmental functions. Additionally, this review focuses on KAT8's roles in cellular homeostasis, stem cell identity, DNA damage repair, and immune response, highlighting its potential as a therapeutic target. The implications of KAT8 in health and disease, as evidenced by recent studies, affirm its importance in cellular physiology and human pathology.

Immobilization of Adenosine Derivatives onto Cellulose Nanocrystals via Click Chemistry for Biocatalysis Applications.

Adenosine triphosphate (ATP) is a central molecule of organisms and is involved in many biological processes. It is also widely used in biocatalytic processes, especially as a substrate and precursor of many cofactors─such as nicotinamide adenine dinucleotide phosphate (NADP(H)), coenzyme A (CoA), and S-adenosylmethionine (SAM). Despite its great scientific interest and pivotal role, its use in industrial processes is impeded by its prohibitory cost. To overcome this limitation, we developed a greener synthesis of adenosine derivatives and efficiently selectively grafted them onto organic nanoparticles. In this study, cellulose nanocrystals were used as a model combined with click chemistry via a copper-catalyzed azide/alkyne cycloaddition reaction (CuAAC). The grafted adenosine triphosphate derivative fully retains its biocatalytic capability, enabling heterobiocatalysis for modern biochemical processes.

RAFT Polymerisation by the Radical Decarboxylation of Carboxylic Acids.

The controlled grafting of polymers from small- and macro-molecular substrates is an essential process for many advanced polymer applications. This usually requires the pre-functionalisation of substrates with an appropriate functional group, such as a RAFT agent or ATRP initiator, which requires additional synthetic steps. In this paper, we describe the direct grafting of RAFT polymers from carboxylate containing small molecules and polymers via photochemical radical decarboxylation. This method utilises the innate functional groups present in the substrates, and achieves efficient polymer initiation in a single step with excellent control of molecular weight and dispersity.

Effectiveness of PrEPTECH: Findings From a 180-Day Randomized Controlled Trial of a Pre-Exposure Prophylaxis Telehealth Intervention.

BACKGROUND: Telehealth approaches are increasingly being used to provide access to pre-exposure prophylaxis (PrEP), an effective but underused HIV prevention modality. This randomized controlled trial of PrEPTECH, a telehealth intervention for the provision of HIV PrEP, seeks to assess its effects on PrEP access. METHODS: Young men who have sex with men and transgender women in Florida and California with an indication for PrEP were randomly assigned in a 1:1 allocation to receive access to PrEPTECH or a control condition, access to an online listing of PrEP resources in their communities. This intent-to-treat analysis used logistic and linear regression to compare self-reported PrEP initiation, use, and coverage between control and intervention arm participants at 90 days and 180 days of follow-up. RESULTS: A total of 229 participants with a mean age of 23.7 years, 77.3% people of color enrolled in PrEPTECH. At 90 days, postbaseline initiation of PrEP was significantly higher among those in the PrEPTECH arm than among controls (odds ratio [OR]: 6.63, 95% confidence interval [CI]: 2.54 to 17.35), and this held true by 180 days post baseline. The count of sex acts for which participants were not protected by PrEP, PrEP adherence, and recent PrEP use at 180 days post baseline were not significantly different between the study arms. CONCLUSIONS: Receiving access to a telehealth platform for PrEP access increased PrEP initiation in this cohort of young, predominantly non-White sexual and gender minorities. PrEP telehealth may be a worthy avenue for providing access to PrEP for these populations, but additional strategies may be needed to promote adherence and persistence of PrEP use.

Effect of temperature on the conformation and functionality of poly(N-isopropylacrylamide) (PNIPAM)-grafted nanocellulose hydrogels.

HYPOTHESIS: Poly(N-isopropylacrylamide) [PNIPAM]-grafted cellulose nanofibers (CNFs) are new thermo-responsive hydrogels which can be used for a wide range of applications. Currently, there is no clear understanding of the precise mechanism by which CNFs and PNIPAM interact together. Here, we hypothesize that the physical crosslinking of grafted PNIPAM on CNF inhibits the free movement of individual CNF, which increases the gel strength while sustaining its thermo-responsive properties. EXPERIMENTS: The thermo-responsive behaviour of PNIPAM-grafted CNFs (PNIPAM-g-CNFs), synthesized via silver-catalyzed decarboxylative radical polymerization, and PNIPAM-blended CNFs (PNIPAM-b-CNFs) was studied. Small angle neutron scattering (SANS) combined with Ultra-SANS (USANS) revealed the nano to microscale conformation changes of these polymer hybrids as a function of temperature. The effect of temperature on the optical and viscoelastic properties of hydrogels was also investigated. FINDINGS: Grafting PNIPAM from CNFs shifted the lower critical solution temperature (LCST) from 32 °C to 36 °C. Below LCST, the PNIPAM chains in PNIPAM-g-CNF sustain an open conformation and poor interaction with CNF, and exhibit water-like behaviour. At and above LCST, the PNIPAM chains change conformation to entangle and aggregate nearby CNFs. Large voids are formed in solution between the aggregated PNIPAM-CNF walls. In comparison, PNIPAM-b-CNF sustains liquid-like behaviour below LCST. At and above LCST, the blended PNIPAM phase separates from CNF to form large aggregates which do not affect CNF network and thus PNIPAM-b-CNF demonstrates low viscosity. Understanding of temperature-dependent conformation of PNIPAM-g-CNFs engineer thermo-responsive hydrogels for biomedical and functional applications.

Additive manufacturing against the Covid-19 pandemic: a technological model for the adaptability and networking.

This investigation analyzes the main contributions that additive manufacturing (AM) technology provides to the world in fighting against the pandemic COVID-19 from a materials and applications perspective. With this aim, different sources, which include academic reports, initiatives, and industrial companies, have been systematically analyzed. The AM technology applications include protective masks, mechanical ventilator parts, social distancing signage, and parts for detection and disinfection equipment (Ju, 2020). There is a substantially increased number of contributions from AM technology to this global issue, which is expected to continuously increase until a sound solution is found. The materials and manufacturing technologies in addition to the current challenges and opportunities were analyzed as well. These contributions came from a lot of countries, which can be used as a future model to work in massive collaboration, technology networking, and adaptability, all lined up to provide potential solutions for some of the biggest challenges the human society might face in the future.

Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond.

BACKGROUND: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. OBJECTIVE: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients' quality of life by addressing unmet needs. METHODS: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. RESULTS: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. CONCLUSIONS: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders.

Thermoresponsive Poly(N-isopropylacrylamide) Grafted from Cellulose Nanofibers via Silver-Promoted Decarboxylative Radical Polymerization.

A family of thermoresponsive poly(N-isopropylacrylamide) [PNIPAM]-grafted cellulose nanofibers (CNFs) was synthesized via a novel silver-promoted decarboxylative polymerization approach. This method relies on the oxidative decarboxylation of carboxylic acid groups to initiate free radicals on the surface of CNFs. The polymerization reaction employs relatively mild reaction conditions and can be performed in a one-step, one-pot fashion. This rapid reaction forms a C─C bond between CNF and PNIPAM, along with the formation of free polymer in solution. The degree of functionalization (DF) and the amount of PNIPAM grafted can be controlled by the Ag concentration in the reaction. Similar to native bulk PNIPAM, PNIPAM-grafted CNFs (PNIPAM-g-CNFs) show remarkable thermoresponsive properties, albeit exhibiting a slight hysteresis between the heating and cooling stages. Grafting PNIPAM from CNFs changes its cloud point from about 32 to 36 °C, influenced by the hydrophilic nature of CNFs. Unlike physical blending, covalently tethering PNIPAM transforms the originally inert CNFs into thermosensitive biomaterials. The Ag concentration used does not significantly change the cloud point of PNIPAM-g-CNFs, while the cloud point slightly decreases with fiber concentration. Rheological studies demonstrated the sol-gel transition of PNIPAM-g-CNFs and revealed that the storage modulus (G') above cloud point increases with the amount of PNIPAM grafted. The novel chemistry developed paves the way for the polymerization of any vinyl monomer from the surface of CNFs and carbohydrates. This study validates a novel approach to graft PNIPAM from CNFs for the synthesis of new thermoresponsive and transparent hydrogels for a wide range of applications.

Nanocrystallisation and self-assembly of biosourced ferulic acid derivative in polylactic acid elastomeric blends.

HYPOTHESIS: The crystallisation of biosourced ferulic acid derivatives - Bis-O-feruloyl-1,4-butanediol (BDF) - in a polylactic acid (PLA) matrix produces thermoplastic elastomeric blends that are transparent and biodegradable. Elastomeric and transparency are controlled by the domain size. PLA-BDF blends up to a threshold BDF concentration providing elastomeric properties show no evidence of BDF crystallisation. Heat treatment weakens the PLA-BDF interaction, give BDF molecules mobility to interact with nearby BDF molecules, leading to BDF nano-crystallisation. EXPERIMENTS: PLA-BDF blends were synthesised by hot-melt processing by mixing pure PLA with different concentrations of BDF (0-40 wt%) at 180 °C for 13 min. One set of blends was annealed at 50 °C for 24 h and compared with the unannealed set. The BDF crystallisation in the blends is studied by combining SAXS, SEM, XRD and Polarised Optical Microscopy. Monte-Carlo simulations were performed to validate SAXS data analysis. FINDINGS: Unannealed PLA-BDF blends of up to the threshold of 20 wt% BDF are dominated by the semicrystalline behaviour of PLA, without any trace of BDF crystallisation. Surprisingly, the PLA-BDF 40 wt% blend shows BDF crystallisation in the form of large and nanoscale structures bonded together by weak interparticle interaction. At concentrations up to 20 wt%, the BDF molecules are homogenously dispersed and bonded with PLA. Increasing BDF to 40 wt% brings the BDF molecules close enough to crystallise at room temperature, as the BDF molecules are still bonded with the PLA network. Annealing of PLA-BDF blends led to BDF nanocrystallisation and self-assembling in the PLA network. Both BDF nanoparticle size and interparticle distance decrease as the BDF concentration increases. However, the number density of BDF nanocrystals increases. The formed BDF nanocrystals have size ranging between 100 and 380 Å with interparticle distance of 120-180 Å. The structure factor and potential mean force confirm the strong interparticle interaction at the higher BDF concentration. Heat treatment weakens the PLA -BDF interaction, which provides mobility to the BDF molecules to change conformation and interact with the nearby BDF molecules, leading to BDF crystallisation. This novel BDF crystallisation and self-assembly mechanism can be used to develop biodegradable shape memory PLA blends for biomedical, shape memory, packaging and energy applications.

[Causes and treatment of anaphylaxis in a Mexican third-level pediatric hospital]. / Causas y tratamiento de anafilaxia en un hospital pediátrico mexicano de tercer nivel.

OBJECTIVE: To clinically characterize the events of anaphylaxis in a third-level pediatric hospital. METHODS: 1148 clinical records were reviewed. Eventually, the information of 35 events of anaphylaxis in 20 patients was analyzed; three of them had multiple episodes of anaphylaxis. RESULTS: The median age for the anaphylactic episodes was 11 years (Interquartile range 10 years, Q1 = 5, Q3 = 15), predominantly in adolescents between the ages of 12 and 17 years, and there was a slight predominance in women. The most frequent clinical manifestations were cutaneous (86%), followed by respiratory (83%), cardiovascular (74%), and gastrointestinal (46%) alterations. Cardiac arrest was documented in three episodes; however, no anaphylaxis-related deaths were reported. The main triggers for anaphylaxis were food (34%), medications (29%), allergen-specific immunotherapy (14%), and latex (11%). In patients with perioperative anaphylaxis, the clinical behavior was severe. Epinephrine was administered in 27 out of the 35 events (77%), but only in 11 cases it was the first-line treatment. Systemic corticosteroids were the most frequently used treatment, followed by epinephrine and antihistamines. CONCLUSIONS: The use of epinephrine, which is the mainstay of the treatment, is suboptimal; with a preferred use of second-line medications like corticosteroids. Clear protocols for the diagnosis and treatment of anaphylaxis, as well as continuous education of health personnel, are necessary.

Objetivo: Caracterizar clínicamente los eventos de anafilaxia en un hospital pediátrico de tercer nivel. Métodos: Se revisaron 1148 expedientes clínicos. Finalmente, se analizó la información correspondiente a 35 episodios de anafilaxia en 20 pacientes; tres de ellos con múltiples episodios de anafilaxia. Resultados: La edad mediana de los episodios de anafilaxia fue de 11 años (rango intercuartilar 10 años, Q1 = 5, Q3 = 15), con predomino en adolescentes de 12 a 17 años y del sexo femenino. Las manifestaciones clínicas más frecuentes fueron las cutáneas (86 %), seguidas de las respiratorias (83 %), las cardiovasculares (74 %) y las gastrointestinales (46 %). En tres casos se documentó paro cardiorrespiratorio, pero no hubo casos de mortalidad asociada a anafilaxia. Los principales desencadenantes fueron alimentos (34 %), medicamentos (29 %), inmunoterapia para alérgenos (14 %) y látex (11 %). En los pacientes con anafilaxia perioperatoria el comportamiento clínico fue grave. La adrenalina se utilizó en 27 de los 35 episodios (77 %), en 11 de ellos fue el tratamiento de primera elección. Los corticosteroides sistémicos fueron los medicamentos más frecuentemente utilizados, seguidos de la adrenalina y los antihistamínicos. Conclusiones: El uso de adrenalina, pilar del tratamiento de anafilaxia, es subóptimo; con uso preferente de medicamentos de segunda línea como los corticosteroides. Se requieren protocolos para diagnóstico y tratamiento de anafilaxia, aunado a una educación continua del personal de salud.

Post-COVID seizure: A new feature of "long-COVID".

Novel coronavirus SARS-CoV-2 has created unprecedented healthcare challenges. Neurologic deficits are often an important presenting symptom. To date, the only reported post-infectious COVID-19 manifestations of neurologic disease include cognitive deficits and dysfunction of the peripheral nervous system. Here we report that seizure can also be a post-COVID-19 or "long-COVID" complication. We present a 71-year-old man with hypertension, diabetes mellitus, and COVID-19 diagnosed by RT-PCR who initially presented with posterior circulation stroke-like symptoms, which completely resolved after emergent thrombolysis. Six days later, the patient returned with seizure activity, supported by radiographic and electroencephalographic studies. Notably, he was negative for SARS-CoV-2, and no other provoking factor was uncovered after a comprehensive work-up. To our knowledge, this is the first report of post-infectious seizures after a case of COVID-19, highlighting the potential importance of monitoring for neurologic symptoms in COVID-19 patients, even after convalescence.

AngioVac thrombectomy in patient with right atrial thrombus and gastrointestinal bleed: case and literature review.

Catheter-directed thrombectomy is a novel promising therapy with little published experience. Previous reports have described it as a useful tool in high risk patients in need of intravascular material resection. Here we present a unique and never reported case of AngioVac device thrombectomy use in a patient with right atrial catheter-associated thrombus and gastrointestinal bleed that contraindicated other thrombectomy therapies due to severe anemia and high bleeding risk. A brief literature review about this therapy and its main outcomes is presented to contextualize the reader and contribute to academic knowledge.

A Combined Strategy of Additive Manufacturing to Support Multidisciplinary Education in Arts, Biology, and Engineering.

This research presents results for the design and creation of supporting teaching materials using additive manufacturing. The materials are inspired by selected artwork of four animal species, which belong to a collection from the museum of the University of Antioquia. The topic selected was fauna in Colombia, and the animals in question were chosen based on important roles they have in areas like health, the environment, and food. These animals will complement science education given to several age groups visiting the museum. In addition to the 3D-manufactured objects, a study was conducted using several age groups that are very relevant to the museum: children, teenagers, and first year undergraduate students. A video showing technical information cards about the manufacturing process was also developed. This project was multidisciplinary, involving collaboration between the engineering school, the museum, and a local high school. The results showed that young visitors want complete information on the animals and to have interaction with the animal models, which is not always possible. This project serves as a local strategy not only for taking arts and knowledge out of the museum but also for planning first year courses in the university and thus reducing problems like school dropout, low motivation, and poor performance in national exams.

Grafting Nature-Inspired and Bio-Based Phenolic Esters onto Cellulose Nanocrystals Gives Biomaterials with Photostable Anti-UV Properties.

Invited for this month's cover is the international collaborative work from the Bioresource Processing Research Institute of Australia (BioPRIA)-Monash University and URD Agro-Biotechnologies Industrielles (ABI)-AgroParisTech. The cover image shows how the grafting of Nature-inspired and bio-based phenolic esters on cellulose nanocrystals through click-chemistry provides materials with highly photostable UV-blocking properties. Cover art by David Mendoza. The Full Paper itself is available at 10.1002/cssc.202002017.

Grafting Nature-Inspired and Bio-Based Phenolic Esters onto Cellulose Nanocrystals Gives Biomaterials with Photostable Anti-UV Properties.

New nature-inspired and plant-derived p-hydroxycinnamate esters and p-hydroxycinnamate diesters provide excellent protection against UV radiation when incorporated into a matrix. Herein, an efficient and sustainable pathway is reported to graft these phenolic compounds onto cellulose nanocrystals (CNCs) via click-type copper-catalyzed azide/alkyne cycloaddition (CuAAC) reaction. The successful grafting of the phenolic esters on CNC surface was evidenced by a range of chemical analyses, and the degrees of substitution (DS) of the CNC were found to depend on the structure of the phenolic ester grafted. Moreover, aqueous suspensions of the phenolic ester-grafted CNCs not only strongly absorb in both the UVA and UVB regions, but they also exhibit average to very high photostability. Their wide spectrum UV-absorbing properties and their stability upon exposure to UV are highly influenced by the structure of the phenolic ester, particularly by the extra ester group in p-hydroxycinnamate diesters. These findings demonstrate that cellulose nanocrystals decorated with such plant-derived and nature-inspired phenolic esters are promising sustainable nanomaterials for anti-UV applications.

Primary Lymphoma Presenting in an Ascending Aortic Aneurysm: A Case Report.

Small lymphocytic lymphoma (SLL) is rarely associated with thoracic aortic aneurysms. Aneurysm of the ascending aorta associated with SLL has never been reported before. We describe the case of an asymptomatic 68-year-old woman who presented with a 5.5-cm aneurysm of the ascending aorta and no prior history of hematological disorders. Following excision and repair, the surgical specimen showed infiltration of the aortic wall by lymphocytes, expressing markers consistent with SLL. While symptomatic SLL carries a poor prognosis, risk stratification tools are applied to guide management strategies in asymptomatic patients.

Controlling the transparency and rheology of nanocellulose gels with the extent of carboxylation.

TEMPO and periodate are combined in a one-shot reaction to oxidise cellulose and produce nanocellulose gels with a wide range of degree of substitution (DS). Highly-oxidised cellulose nanofibres with a high charge of -80 mV were produced. The strong electrical repulsion between TEMPO-periodate oxidised nanofibres (TPOF) results in the formation of well-separated nanofibres with a diameter of 2-4 nm, albeit depolymerised due to high oxidation. TPOF produces highly-transparent gels due to smaller aspect ratio and high surface charge. These properties induce a reduced viscosity and moduli of the gels by decreasing fibre entanglement. TPOF gels are more stable at basic pH and high ionic strength than TEMPO-oxidised gels due to their higher surface charge. Freeze-dried TPOF gels also exhibit remarkable water holding capacity due to enhanced immobilisation of water molecules. The excellent optical properties of the highly transparent gel for red blood cells analysis open new possibilities in diagnostics application.

One-shot TEMPO-periodate oxidation of native cellulose.

TEMPO/NaClO/NaBr and sodium periodate were combined in a one-shot reaction to oxidise cellulose from bleached pulp. Oxidation of cellulose forms two fractions: a highly-carboxylated water-insoluble (up to 1.9 mmol COO-/g, DS = 0.39) and a water-soluble fraction (up to 4 mmol COO-/g, DS = 1.1). Results show that these regioselective oxidants work in synergy to produce fully-oxidised 2,3,6-tricarboxycellulose. Increasing the periodate concentration results in fibrillation and extensive depolymerisation of the pulp cellulose as more residual aldehyde groups participate in the depolymerisation process. X-ray diffraction (XRD) reveals that the addition of periodate increases cellulose crystallinity, retains crystal size but slightly alters the XRD pattern. The degree of substitution (DS), which governs the solubility of carboxylated cellulose, can be controlled by varying the periodate concentration. Combining TEMPO/NaBr/NaClO with sodium periodate simultaneously in a one-shot reaction produces low-cost cellulose with controlled level of carboxylation and unique properties.

Severe Neonatal RYR1 Myopathy With Pathological Features of Congenital Muscular Dystrophy.

The phenotypes associated with pathogenic variants in the ryanodine receptor 1 gene (RYR1, OMIM# 180901) have greatly expanded over the last few decades as genetic testing for RYR1 variants has become more common. Initially described in association with malignant hyperthermia, pathogenic variants in RYR1 are typically associated with core pathology in muscle biopsies (central core disease or multiminicore disease) and symptomatic myopathies with symptoms ranging from mild weakness to perinatal lethality. We describe a 2-week-old male patient with multiple congenital dysmorphisms, severe perinatal weakness, and subsequent demise, whose histopathology on autopsy was consistent with congenital muscular dystrophy. Immunohistochemical analysis of dystrophy-associated proteins was normal. Rapid exome sequencing revealed a novel heterozygous nonsense variant (p.Trp661Ter) in RYR1, as well as a previously described RYR1 pathogenic variant associated with congenital myopathy (p.Phe4976Leu). This highlights the potential for RYR1 pathogenic variants to produce pathological findings most consistent with congenital muscular dystrophy.